The taste modality is critical not only to aid in the identification of food, but also to avoid consuming noxious chemicals. The long-term goal of the proposed research is to understand the molecular mechanisms underlying sweet and bitter taste transduction in the fruitfly, Drosophila melanogaster. The fruitfly has proven to be a valuable model organism for characterizing other sensory modalities, such as vision and olfaction;however, taste transduction has received less scrutiny. Recent studies indicate that the mammalian and Drosophila taste transduction pathways are initiated by G- protein coupled receptors. However, the mechanisms operating downstream of the Drosophila receptors are largely unknown. In mammals, there is evidence that taste transduction operates through a phospholipase C mediated signaling pathway that culminates with the activation of the TRPM5 channel. Nevertheless, many questions remain including the mechanisms of adaptation, the role of cAMP signaling in taste transduction, the mechanisms that regulate the gustatory channel in vivo and the proteins regulating the gustatory receptors. The goal,of the proposed research is to apply a combination of genetic, electrophysiological, cell and biochemical approaches in Drosophila to define the biochemical basis for taste transduction initiated by either attractive or aversive compounds. The specific aims of this proposal are to test the hypotheses that: 1) the PI signaling proteins involved in Drosophila vision also function in taste, 2) cAMP signaling functions in Drosophila sweet and bitter transduction, 3) Gr66a is the caffeine receptor and misexpression of this receptor can elicit an attractive behavioral response to caffeine, and 4) the TRPA2 gustatory channel is regulated by calmodulin and interactions with the scaffold protein Homer. Given the apparent parallels between mammalian and Drosophila taste transduction, these studies should provide important new insights into the mechanisms of gustatory transduction that apply to human taste receptor cells.